Cigarette smoking costs an estimated 418,000 American lives annually. Cessation reduces this cost, but is difficult because smoking is maintained by factors such as withdrawal, tobacco's direct effects, and smoking-related stimuli. Current cessation methods address these factors: nicotine replacement treatments (NRTs) suppress withdrawal and/or blunt the effects of cigarettes. Behavioral treatments reduce the influence of smoking-related stimuli. Nonetheless, about 70 percent of smokers who try to quit, fail. Improving smoking cessation rates is a national priority that may be achieved by tailoring treatment to the separate needs of subgroups, such as men and women. Treatment studies demonstrate that current cessation techniques are less effective for women. There is no clear explanation for this difference, but it may involve a differential response NRT and/or smoking-related stimuli. For women, NRT may be less effective at suppressing withdrawal (Hypothesis 1) or blunting the effects of smoking during a quit attempt (Hypothesis 2). Women may also be more sensitive to smoking-related stimuli, such as the taste, sight, and smell of smoke (Hypothesis 3). These hypotheses can be examined efficiently in the clinical laboratory. Strengths of this setting include control over extraneous variables, repeated measure designs that yield dose effect curves, and validated tools for measuring puff topography, tobacco withdrawal, and the direct effects of nicotine and/or cigarettes. Three such studies are proposed. In each study, 64 men and 64 women who smoke will participate in 4 double blind, randomly ordered, 6.5-hour sessions. Objectively verified cigarette abstinence will be required before each session. Studies 1 and 2 will compare, in men and women, the NRT dose response functions for suppression of tobacco and blunting the effects of cigarettes; study 3 will compare the effects of smoking-related stimuli. Thus hypotheses 1, 2, and 3 are each addressed in separate studies. Overall, this project may improve cessation interventions for all smokers, particularly women. Given the costs of smoking and the dramatic reduction in these costs when smokers quit smoking, improving the treatment options for all smokers is essential.